Purified group A streptococcal pyrogenic exotoxins (SPE) A, B, and C will be used for all proposed investigations. A radioimmunoassay will be developed for measuring serum levels of antitoxin. Various techniques, particularly glutaraldehyde polymerization, for detoxification and preparation of multivalent toxoids ultimately to be used for human immunization will be examined. Amino acid sequencing of SPE C will continue and may reveal homologies between the toxin and known peptide hormones. The lymphocyte target of the SPE both for nonspecific mitogenicity and immunosuppression will be studied. Studies will continue relating to the genetic mechanisms, including transduction, transformation, and plasmids in the control of SPE production. The molecular mechanism of enhancement of lethal endotoxin shock and myocardial damage will be studied with the intent of identifying the target affected by SPE. It is hoped that elucidation of this mechanism may be applied also to the other biological effects of the toxins. Using a variety of cell types, including lymphocytic, liver, myocardial, and hypothalamic studies of toxin-receptor interactions will be initiated.